Monica V. Horn

Living-donor lobar lung transplantation experience: Intermediate results

OBJECTIVE Living-donor lobar lung transplantation offers an alternative for patients with a life expectancy of less than a few months. We report on our intermediate results with respect to recipient survival, complications, pulmonary function, and hemodynamic reserve. METHODS Thirty-eight living-donor lobar lung transplants were performed in 27 adult and 10 pediatric patients for cystic fibrosis (32), pulmonary hypertension (two), pulmonary fibrosis (one), viral bronchiolitis (one), bronchopulmonary dysplasia (one), and posttransplantation obliterative bronchiolitis (one). Seventy-six donors underwent donor lobectomies. RESULTS There were 14 deaths among the 37 patients, with an average follow-up of 14 months. Predominant cause of death was infection, consistent with the large percentage of patients with cystic fibrosis in our population. The overall incidence of rejection was 0.07 episodes/patient-month, representing 0.8 episodes/patient. Postoperative pulmonary function testing generally showed a steady improvement that plateaued by postoperative months 9 to 12. Fourteen patients who were followed up for at least 1 year underwent right heart catheterization; pressures and pulmonary vascular resistances were within normal ranges. Bronchiolitis obliterans was definitively diagnosed in three patients. Among the 76 donors, complications in the postoperative period included postpericardiotomy syndrome (three), atrial fibrillation (one), and surgical reexploration (three). CONCLUSIONS We believe that these data support an expanded role for living-donor lobar lung transplantation. Our intermediate data are encouraging with respect to the functional outcome and survival of these critically ill patients, who would have died without this option.

Comparison of outcomes between living donor and cadaveric lung transplantation in children.

BACKGROUND Long-term survival in lung transplant is limited by bronchiolitis obliterans (BOS). We compared outcomes in pediatric living donor bilateral lobar (LL) vs cadaveric lung transplant (CL). METHODS Children were studied who had LL or CL with at least 1 year follow-up. Data collected included acute rejection episodes, pulmonary function tests (PFT), BOS, and survival. Mean age was 13.36+/-3.16 years in LL and 12.00+/-4.19 years in CL patients (p = 0.37, ns). RESULTS There was no difference in rejection (p = 0.41, ns). CL had rejection earlier (2.48+/-3.84 months) than LL (13.60+/-10.74 months; p = 0.02). There was no difference in 12 month PFT. But at 24 months, LL had greater forced expiratory volume in 1 second (FEV1) (p = 0.001) and FEF25-71% (p = 0.01) than CL. BOS was found in 0/14 LL vs 9/11 (82%) CL after 1 year (p = 0.04). After 2 years, 0/8 LL and 6/7 (86%) CL had BOS (p < 0.05). LL had 85% survival vs 79% for CL at 12 months. At 24 months, LL survival was 77% vs 67% for CL. CONCLUSIONS Pediatric LL had less BOS and better pulmonary function than CL. As BOS is a determinant of long-term outcome, we believe LL is the preferred lung transplant method for children.

A Decade of Living Lobar Lung Transplantation: Perioperative Complications after 253 Donor Lobectomies†

Living lobar lung transplantation places two donors at risk for each recipient. We examined the perioperative outcomes associated with the 253 donor lobectomies performed at our institution during our first decade of living lobar lung transplantation. There have been no perioperative or long‐term deaths. 80.2% of donors (n = 203) had no perioperative complications, while fifty (19.8%) had one or more complication. The incidence of intraoperative complications was 3.6%. Complications requiring reoperation occurred in 3.2% of donors. 15.0% of donors had other perioperative complications; the most serious were two donors who developed pulmonary artery thrombosis, while the most common was the need for an additional thoracostomy tube or a thoracostomy tube for ≥14 d for persistent air leaks and/or drainage. Right‐sided donors were more likely to have a perioperative complication than left‐sided donors (odd ratio 2.02, p = 0.04), probably secondary to right lower and middle lobe anatomy. This experience has shown donor lobectomy to be associated with a relatively low morbidity and no mortality, and is important if this procedure is to be considered an option at more pulmonary transplant centers, given continued organ shortages and differences in philosophical and ethical acceptance of live

Experience with living-donor lobar transplantation for indications other than cystic fibrosis.

OBJECTIVE Since development of a living donor bilateral lobar transplantation protocol for patients with cystic fibrosis, our indications have expanded to include recipients with other diagnoses. METHODS We report on our experience in eight patients with primary pulmonary hypertension, postchemotherapy pulmonary fibrosis, bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and obliterative bronchiolitis. The average age of the eight patients was 19.1 years (range 9 to 40). The mean preoperative carbon dioxide tension for the four patients who did not have primary pulmonary hypertension was 92 mm Hg (range 64 to 120 mm Hg), and the two patients with pulmonary fibrosis were intubated (one on high-frequency jet ventilation). Each recipient received a right lower lobe (n = 7) or middle lobe (n = 1) and a left lower lobe (n = 8) from a total of 16 donors representing various combinations of the recipients family (n = 15) and an unrelated friend (n = 1). RESULTS With an average follow-up of 1 year the overall survival is 75%. For the five patients followed up for at least 1 year, mean forced vital capacity was 80.6%, forced expiratory volume in 1 second was 75.6%, mid-forced expiratory flow was 64%, and diffusing lung capacity corrected for alveolar volume was 73% of predicted. For those patients with primary pulmonary hypertension, preoperative hemodynamics revealed mean pressures as follows: blood pressure 84.8 mm Hg, right atrial pressure 7.8 mm Hg, pulmonary artery pressure 71.3 mm Hg, pulmonary capillary wedge pressure 9.5 mm Hg, cardiac index 2.9 L/min per square meter, and pulmonary vascular resistance index 22.8 Wood units. Postoperative hemodynamics revealed a mean blood pressure of 84.3 mm Hg, right atrial pressure of 2.7 mm Hg, pulmonary artery pressure of 16 mm Hg, pulmonary capillary wedge pressure of 7.3 mm Hg, cardiac index of 4.2 L/min per square meter, and pulmonary vascular resistance index of 1.9 Wood units. CONCLUSIONS Early results of living-donor bilateral lobar transplantation for diseases other than cystic fibrosis have resulted in satisfactory survival and pulmonary function. Additionally, patients with severe primary pulmonary hypertension have had dramatic normalization of their hemodynamics despite the limited amount of lung tissue transplanted. We believe that the data from this small cohort experience compares favorably with our larger series with cystic fibrosis and supports an expanded role for living-donor lobar transplantation in patients with alternate indications.

Bordetella bronchiseptica infection in pediatric lung transplant recipients

Abstract: Bordetella bronchiseptica are small, pleomorphic Gram‐negative coccobacilli which are commensal organisms in the upper respiratory tract of many wild and domestic animals (‘kennel cough’ in dogs). While it is common for health care providers to ask about exposure to ill family/friends, most do not routinely inquire about the health or immunization status of household pets. We report two cases of B. bronchiseptica pneumonia in lung transplant recipients [cystic fibrosis (CF); ages 10 and 15 yr; one male] who contracted B. bronchiseptica from pet dogs. We compared their course and outcome to four children (two CF, one congenital heart disease and one Duchennes muscular dystrophy; four males, age range 6 months to 14 yr) with B. bronchiseptica cultured from the respiratory tract. Two of the four patients also acquired their illnesses from pet dogs and two from unknown sources. One lung transplant recipient expired from progressive respiratory failure. We conclude that B. bronchiseptica can cause serious infections in both immunosuppressed and immunocompetent children. We speculate that a detailed history of exposure to ill pets (particularly dogs), and the immunization status of all pets should be included in the routine evaluation of all pediatric transplant recipients.

Psychosocial responses of adolescent cystic fibrosis patients to lung transplantation

Abstract: What psychosocial issues do adolescent cystic fibrosis (CF) patients experience after undergoing lung transplantation (Tx)? The aim of this study was to determine, using an ethnographic study design, the common themes and emotional responses in post‐lung transplant adolescent CF patients of the Cardiothoracic Transplant Clinic at the Childrens Hospital Los Angeles. Nineteen CF lung transplant recipients were studied (eight males, 11 females: mean age at time of transplant, 15.7 ± 2.7 yr). The mean time interval from Tx to interview was 25.4 months (range 1–58 months). Sixteen patients had living donor lobar lung Tx while three patients received cadaveric lungs. A series of 25 questions was used to assess the psychosocial impact of Tx, and a semi‐structured interview focused on the following five domains: lifestyle, family functioning, social functioning, body image, and psychological functioning. The major themes identified by patients included: a strong desire to set and attain meaningful long‐range goals, the need to control as many aspects of their lives as possible while dealing with parental over‐protectiveness, and the adjustment to a new lifestyle. Common emotional responses included manageable fear/anxiety of lung rejection and uncertainty of the future, impatience with disruptions of daily routines caused by post‐transplant medical management and its effect on the attainment of set goals, and frustration with parental over‐protectiveness. In general, patients reported a positive outlook on life, with greater emphasis on sought‐after goals as well as inter‐personal relationships. This study demonstrates that adolescent CF transplant recipients develop long‐term goals and plans for independence. By identifying and anticipating the emotional needs of this population, health care providers can assist patients in improving the quality of their lives from a physiological, as well as a psychological, viewpoint.

Bronchiolitis obliterans is not the primary cause of death in pediatric living donor lobar lung transplant recipients

BACKGROUND Obliterative bronchiolitis (OB) is the chief cause of mortality in cadaveric lung transplant patients (CL). But, is OB the primary cause of mortality for living donor lobar recipients? To answer this question, we reviewed the causes of mortality in our pediatric patients who underwent living donor lobar lung transplantation (LD) and compared them with our pediatric patients who received whole cadaveric lungs (CL). METHODS Data collected included demographics, transplant type, hospital days, immunosuppression regimen, and cause of death. Statistical analysis was done using Fishers Exact test and Students t-test (mean +/- SD). RESULTS From May 1993 to December 1999, 53 patients underwent lung transplantation (21 males, 32 females; mean age 12.4 +/- 5.4 years). Twenty-nine patients had LD procedures (12 males, 17 females; mean age 14.4 +/- 3.6 years) and 24 patients had CL surgery (9 males, 15 females; p = .78 [not significant]; mean age 9.8 +/- 6.3 years; p =.001). All patients received triple immunosuppression without induction. During the study period, 9 LD (6 males, 3 females; mean age 15.7 +/- 5.0 years) and 14 CL (3 males, 11 females; mean age 11.3 +/- 6.9 years) patients died. There was no significant difference between patients in the LD and CL groups who died with regard to gender (p = .08), age at the time of death (p = .12), mortality rate (p = .06), number of hospital days (p = .09), immunosuppressive medications (p > .08), incidence of non-specific graft failure (p = .26), or incidence of infection (p = .18). However, there was a significant difference in the incidence of OB between LD and CL recipients (p = .002). CONCLUSIONS OB was not found to be the chief cause of mortality in pediatric LD recipients. We speculate that prevention of infections, possibly by a modest reduction in immunosuppressive therapy and aggressive antimicrobial therapy, may improve long-term survival in pediatric living donor lobar lung transplant recipients.

Does lung growth occur when mature lobes are transplanted into children

Abstract: Lung volume increases after living donor lobar lung transplantation (LD) in children. The mechanism responsible for this increase may be alveolarization (lung growth) or alveolar dilation. The diffusing capacity of the lung for carbon monoxide adjusted for lung volume (DLco/VA) should decrease if alveolar dilation occurs, but not if lung growth occurs. Pulmonary function tests were measured 1–12 months after transplant in 20 children receiving LD transplants and in 11 children receiving cadaveric whole lung transplantation (CL). One month after transplant there were no differences between LD and CL recipients in age, gender, or height. Compared to the first month after transplant, height increased at 6–12 months after LD (p < 0.05), and only at 12 months after CL (p = 0.02). Total lung capacity (TLC) showed an 11–22% increase at 3–12 months after LD , and an 11–14% increase at 6–12 months after CL. DLco/VA showed an 11–17% decrease at 3–12 months after LD. However, in recipients of CL, DLco/VA showed a transient decrease of 10% at 3–6 months post‐transplant, but was not significantly lower at 9–12 months. LD recipients had lower DLco/VA values than CL recipients at 6–12 months after transplant (p < 0.05). We conclude that following LD, lung volume increases, but DLco/VA decreases. We speculate that alveolar dilation, rather than alveolarization, is the primary mechanism of increased lung volume in children following LD.

Paecilomyces variotii in a pediatric patient with lung transplantation

Abstract: Aspergillus has been noted to be the most common species of filamentous fungus isolated from the airways of lung transplantation (Tx) patients. In general, the bronchi are colonized asymptomatically with Aspergillus but this places such a patient population at greater risk of invasive infection. Other filamentous fungal species may also assume importance in this patient population. Here we report the post‐transplant isolation of Paecilomyces variotii from the airways of a pediatric patient with cystic fibrosis (CF) who underwent bilateral living‐donor lobar lung Tx. This is the first report of isolation of P. variotii in the pediatric lung Tx population. The isolation of filamentous fungi, such as Paecilomyces, with variable in vitro susceptibility to currently available antifungal agents further complicates the approach to post‐transplant antifungal therapy in patients with lung Tx.

What are the best pulmonary function test parameters for early detection of post-lung transplant bronchiolitis obliterans syndrome in children?

Abstract:  Post‐lung transplant bronchiolitis obliterans syndrome (BOS) is defined as an unexplained fall in forced expiratory volume in 1 s (FEV1) ≥20% of baseline (B). There have been reports in adults that FEF25−75% (>30% decline from B) is more sensitive than FEV1 for the early diagnosis of BOS. Yet, it is not known if other pulmonary function test (PFT) parameters – forced expiratory flow rates at 25–75% of vital capacity (FEF25−75%) and maximal expiratory flow rate at 80% (Vmax80%), 70% (Vmax70%) and 60% (Vmax60%) – are more sensitive indicators for early diagnosis of BOS than FEV1 in post‐lung transplant children. We reviewed serial PFTs of 18 patients (ages 14.1 ± 3.7 yr, 50% female) who had lung transplantation at our institution from 1993 to 1999, and who met the criteria for BOS diagnosis. There was no significant difference in post‐transplant days when decline in FEV1 ≥20% of B, FEF25−75% >30% of B, and Vmax80%, Vmax70% and Vmax60% from normal occurred (635 ± 431, 551 ± 422 and 454 ± 287 days, respectively; p = 0.4). However, a decline in FEV1 was the first abnormality in only 39% of the patients, while a decline in FEF25−75% and Vmax at specific lung volume were the first abnormality in 78% and 56% of the patients, respectively. The earliest signs of BOS would be missed in 61% of patients if FEV1 was the primary parameter used for the diagnosis. In order to improve the sensitivity of the diagnosis of post‐lung transplant BOS; we speculate that the diagnosis should be based on decreases in FEF25−75% rather than on FEV1.